Dementia Subtypes Defined Through Neuropsychiatric Symptom-Associated Brain Connectivity Patterns.

Importance: Understanding the heterogeneity of neuropsychiatric symptoms (NPSs) and associated brain abnormalities is essential for effective management and treatment of dementia. Objective: To identify dementia subtypes with distinct functional connectivity associated with neuropsychiatric subsyndromes. Design, Setting, and Participants: Using data from the Open Access Series of Imaging Studies-3 (OASIS-3; recruitment began in 2005) and Alzheimer Disease Neuroimaging Initiative (ADNI; recruitment began in 2004) databases, this cross-sectional study analyzed resting-state functional magnetic resonance imaging (fMRI) scans, clinical assessments, and neuropsychological measures of participants aged 42 to 95 years. The fMRI data were processed from July 2022 to February 2024, with secondary analysis conducted from August 2022 to March 2024. Participants without medical conditions or medical contraindications for MRI were recruited. Main Outcomes and Measures: A multivariate sparse canonical correlation analysis was conducted to identify functional connectivity-informed NPS subsyndromes, including behavioral and anxiety subsyndromes. Subsequently, a clustering analysis was performed on obtained latent connectivity profiles to reveal neurophysiological subtypes, and differences in abnormal connectivity and phenotypic profiles between subtypes were examined. Results: Among 1098 participants in OASIS-3, 177 individuals who had fMRI and at least 1 NPS at baseline were included (78 female [44.1%]; median [IQR] age, 72 [67-78] years) as a discovery dataset. There were 2 neuropsychiatric subsyndromes identified: behavioral (r = 0.22; P = .002; P for permutation = .007) and anxiety (r = 0.19; P = .01; P for permutation = .006) subsyndromes from connectivity NPS-associated latent features. The behavioral subsyndrome was characterized by connections predominantly involving the default mode (within-network contribution by summed correlation coefficients = 54) and somatomotor (within-network contribution = 58) networks and NPSs involving nighttime behavior disturbance (R = -0.29; P < .001), agitation (R = -0.28; P = .001), and apathy (R = -0.23; P = .007). The anxiety subsyndrome mainly consisted of connections involving the visual network (within-network contribution = 53) and anxiety-related NPSs (R = 0.36; P < .001). By clustering individuals along these 2 subsyndrome-associated connectivity latent features, 3 subtypes were found (subtype 1: 45 participants; subtype 2: 43 participants; subtype 3: 66 participants). Patients with dementia of subtype 3 exhibited similar brain connectivity and cognitive behavior patterns to those of healthy individuals. However, patients with dementia of subtypes 1 and 2 had different dysfunctional connectivity profiles involving the frontoparietal control network (FPC) and somatomotor network (the difference by summed z values was 230 within the SMN and 173 between the SMN and FPC for subtype 1 and 473 between the SMN and visual network for subtype 2) compared with those of healthy individuals. These dysfunctional connectivity patterns were associated with differences in baseline dementia severity (eg, the median [IQR] of the total score of NPSs was 2 [2-7] for subtype 3 vs 6 [3-8] for subtype 1; P = .04 and 5.5 [3-11] for subtype 2; P = .03) and longitudinal progression of cognitive impairment and behavioral dysfunction (eg, the overall interaction association between time and subtypes to orientation was F = 4.88; P = .008; using the time × subtype 3 interaction item as the reference level: ß = 0.05; t = 2.6 for time × subtype 2; P = .01). These findings were further validated using a replication dataset of 193 participants (127 female [65.8%]; median [IQR] age, 74 [69-77] years) consisting of 154 newly released participants from OASIS-3 and 39 participants from ADNI. Conclusions and Relevance: These findings may provide a novel framework to disentangle the neuropsychiatric and brain functional heterogeneity of dementia, offering a promising avenue to improve clinical management and facilitate the timely development of targeted interventions for patients with dementia.

Similar Quality of Visual Working Memory Representations between Negative and Positive Attentional Templates.

Visual working memory (VWM) plays an important role during visual search, with some theories suggesting an equivalence between working memory representations and guidance from attentional templates. However, recent work has shown that participants can also use 'negative templates', the foreknowledge of distractor-features stored in VWM, to guide attention away from distractors during visual search. These negative templates must also be represented in working memory, but the question remains whether the quality of the working memory representations underlying negative and positive templates are similar, in spite of their opposite impacts on attention. In this study, participants (N = 33) engaged in a visual search task for a shape-defined target after receiving a positive cue (target color), negative cue (distractor color) or neutral cue (non-informative). In 20% of the trials, a color-wheel probe was presented instead of a search array to measure the quality of the cue representation stored in VWM. Our results revealed that participants were more likely to guess in response to neutral cues than negative cues. Yet, the comparison between positive and negative cues showed no significant differences. However, we found no difference in memory precision for the three cue types. More interestingly, the more the VWM quality is boosted by the negative cue, the greater the ability to guide attention away from distractors. Such a pattern of results might map to recent evidence of between-individuals differences in utilization of negative cues. These findings highlight the distinction between attentional templates and simple maintenance in working memory.

Can We Enhance Shared Decision-making for Periacetabular Osteotomy Surgery? A Qualitative Study of Patient Experiences.

BACKGROUND: Periacetabular osteotomy (PAO) surgery presents an opportunity for shared decision-making (SDM) and may be facilitated by decision-making tools. Currently, no diagnosis or treatment-specific decision-making tools exist for this patient population. Understanding patient PAO surgery decision-making experiences and processes would enable development of a treatment-specific decision-making tool and would help hip preservation surgeons with SDM practices. QUESTIONS/PURPOSES: Qualitative methodology was used to address the following questions: (1) What were the information support needs of adult patients with hip dysplasia who decided to have PAO? (2) What was important to adult patients with hip dysplasia who decided to have PAO? (3) How did adult patients with hip dysplasia who have undergone PAO experience the surgical decision-making process? (4) What elements of SDM did adult patients with hip dysplasia experience with their surgeons when deciding to have PAO? METHODS: Fifteen volunteer, English-speaking patients in the United States who had been diagnosed with hip dysplasia and who had undergone PAO surgery 6 to 12 months prior to the study were recruited through five PAO surgery Facebook support groups. Individuals were excluded if they had an underlying neuromuscular condition or other diagnosis related to nondevelopmental dysplasia of the hip or if they had a previous PAO surgery > 12 months before data collection. We used purposive sampling strategies to promote sample heterogeneity based on age and preoperative activity level, as these are characteristics that may impact decision-making. Participants were categorized into three age groups: 20 to 29 years, 30 to 39 years, and ≥ 40 years. Participants were also categorized as having "low activity," "moderate activity," or "high activity" preoperatively based on self-reported University of California Los Angeles (UCLA) Activity Scale scores. Participants were enrolled consecutively if they met the inclusion criteria and fulfilled one of our sampling categories; we had plans to enroll more participants if thematic saturation was not achieved through the first 15 interviews. Participants included 14 women and one man ranging in age from 23 to 48 years, and all had undergone PAO surgery for hip dysplasia 6 to 12 months prior to the interview. One-on-one semistructured interviews were conducted with each participant by a single interviewer through Zoom video conferencing using video and audio recording. Participants answered semistructured interview questions and provided verbal responses to survey questions so researchers could gain demographic information and details about their symptoms, diagnosis, and PAO surgery between June 2021 and August 2021. Quantitative survey data were analyzed using descriptive statistics. Qualitative data were analyzed by three researchers using principles of reflexive thematic analysis. Candidate themes were iteratively defined and redefined until central themes were developed that were distinctly different, yet centrally relevant, and answered the research questions. All codes that informed category and theme development were generated within the first six transcripts that were analyzed. The team felt that thematic saturation was established with the 15 interviews. RESULTS: The main information needs for adult patients with hip dysplasia included diagnosis and treatment-related information, as well as logistics related to surgery and recovery. Many patients described that their information needs were only partially met by their surgeon; most engaged in additional information-seeking from scientific research and online resources and relied on patient peers to meet information needs about the lived experience and logistics related to surgery and recovery. It was important to patients that PAO surgery could preserve their native hip or delay THA and that PAO surgery was likely to reduce their pain and improve function; decision-making was facilitated when patients were able to identify how the indications and goals of PAO surgery aligned with their own situation and goals for surgery. Patients' experiences with decision-making were more positive when information needs were met, when indications and goals for PAO surgery aligned with their personal values and goals, and when their preferred and actual decision-making roles aligned. Adult patients with hip dysplasia described high variability in the extent to which patients were invited to share personal preferences, values, and goals around PAO surgery and the extent to which preferred patient decision-making roles were assessed. CONCLUSION: We found that elements of SDM are not consistently integrated into hip preservation practice. The knowledge gained through this work about patient PAO surgery information needs, what matters to patients when deciding to have surgery, and their experiences with PAO surgery decision-making can inform future PAO surgery decision-making tool development. Future studies are needed to validate the findings of this study and to determine whether they are generalizable to adult patients with hip dysplasia with different demographic characteristics or to patients who do not participate in social media support groups. CLINICAL RELEVANCE: Surgeons should recognize that patients are likely to leave their office without their information needs being met. SDM strategies can promote more effective information exchanges in the clinic so surgeons can help patients identify their information needs, provide education and direction to accurate and reputable resources to meet those needs, and help patients appraise information they gather and apply it to their personal situation. Hip preservation surgeons can use the sample SDM script and checklist offered here to support adult patients with hip dysplasia who are making PAO surgery decisions until a future diagnosis and treatment-specific decision-making tool is available.

Functional characterization of 2,832 JAG1 variants supports reclassification for Alagille syndrome and improves guidance for clinical variant interpretation.

Pathogenic variants in the JAG1 gene are a primary cause of the multi-system disorder Alagille syndrome. Although variant detection rates are high for this disease, there is uncertainty associated with the classification of missense variants that leads to reduced diagnostic yield. Consequently, up to 85% of reported JAG1 missense variants have uncertain or conflicting classifications. We generated a library of 2,832 JAG1 nucleotide variants within exons 1-7, a region with a high number of reported missense variants, and designed a high-throughput assay to measure JAG1 membrane expression, a requirement for normal function. After calibration using a set of 175 known or predicted pathogenic and benign variants included within the variant library, 486 variants were characterized as functionally abnormal (n = 277 abnormal and n = 209 likely abnormal), of which 439 (90.3%) were missense. We identified divergent membrane expression occurring at specific residues, indicating that loss of the wild-type residue itself does not drive pathogenicity, a finding supported by structural modeling data and with broad implications for clinical variant classification both for Alagille syndrome and globally across other disease genes. Of 144 uncertain variants reported in patients undergoing clinical or research testing, 27 had functionally abnormal membrane expression, and inclusion of our data resulted in the reclassification of 26 to likely pathogenic. Functional evidence augments the classification of genomic variants, reducing uncertainty and improving diagnostics. Inclusion of this repository of functional evidence during JAG1 variant reclassification will significantly affect resolution of variant pathogenicity, making a critical impact on the molecular diagnosis of Alagille syndrome.

Resilience of mental health services amidst Ebola disease outbreaks in Africa.

Introduction: Health systems including mental health (MH) systems are resilient if they protect human life and produce better health outcomes for all during disease outbreaks or epidemics like Ebola disease and their aftermaths. We explored the resilience of MH services amidst Ebola disease outbreaks in Africa; specifically, to (i) describe the pre-, during-, and post-Ebola disease outbreak MH systems in African countries that have experienced Ebola disease outbreaks, (ii) determine the prevalence of three high burden MH disorders and how those prevalences interact with Ebola disease outbreaks, and, (iii) describe the resilience of MH systems in the context of these outbreaks. Methods: This was a scoping review employing an adapted PRISMA statement. We conducted a five-step Boolean strategy with both free text and Medical Subject Headings (MeSH) to search 9 electronic databases and also searched WHO MINDbank and MH Atlas. Results: The literature search yielded 1,230 publications. Twenty-five studies were included involving 13,449 participants. By 2023, 13 African nations had encountered a total of 35 Ebola outbreak events. None of these countries had a metric recorded in MH Atlas to assess the inclusion of MH in emergency plans. The three highest-burden outbreak-associated MH disorders under the MH and Psychosocial Support (MHPSS) framework were depression, post-traumatic stress disorder (PTSD), and anxiety with prevalence ranges of 1.4-7%, 2-90%, and 1.3-88%, respectively. Furthermore, our analysis revealed a concerning lack of resilience within the MH systems, as evidenced by the absence of pre-existing metrics to gauge MH preparedness in emergency plans. Additionally, none of the studies evaluated the resilience of MH services for individuals with pre-existing needs or examined potential post-outbreak degradation in core MH services. Discussion: Our findings revealed an insufficiency of resilience, with no evaluation of services for individuals with pre-existing needs or post-outbreak degradation in core MH services. Strengthening MH resilience guided by evidence-based frameworks must be a priority to mitigate the long-term impacts of epidemics on mental well-being.

Analysis of fetal heart rate fluctuations in women diagnosed with preeclampsia during the latent phase of labor.

Introduction: Fetal heart rate variability (fHRV) is a tool used to investigate the functioning of the fetal autonomic nervous system. Despite the significance of preeclampsia, fHRV during the latent phase of labor has not been extensively studied. This study aimed to evaluate fetal cardiac autonomic activity by using linear and nonlinear indices of fHRV analysis in women diagnosed with preeclampsia without hypertensive treatment during gestation, compared to normotensive women during the latent phase of labor. Methods: A cross-sectional and exploratory study was conducted among pregnant women in the latent phase of labor, forming three study groups: normotensive or control (C, 38.8 ± 1.3 weeks of pregnancy, n = 22), preeclampsia with moderate features (P, 37.6 ± 1.4 weeks of pregnancy n = 10), and preeclampsia with severe features (SP, 36.9 ± 1.2 weeks of pregnancy, n = 12). None of the participants received anti-hypertensive treatment during their pregnancy. Linear and nonlinear features of beat-to-beat fHRV, including temporal, frequency, symbolic dynamics, and entropy measures, were analyzed to compare normotensive and preeclamptic groups. Results: Significantly lower values of multiscale entropy (MSE) and short-term complexity index (Ci) were observed in the preeclamptic groups compared to the C group (p < 0.05). Additionally, higher values of SDNN (standard deviation of R-R intervals) and higher values of low-frequency power (LF) were found in the P group compared to the C group. Conclusion: Our findings indicate that changes in the complexity of fetal heart rate fluctuations may indicate possible disruptions in the autonomic nervous system of fetuses in groups affected by undiagnosed preeclampsia during pregnancy. Reduced complexity and shifts in fetal autonomic cardiac activity could be associated with preeclampsia's pathophysiological mechanisms during the latent phase of labor.

Human skin absorption of three phthalates.

Population studies reveal widespread exposure to phthalates. Understanding their absorption, distribution, metabolism, and excretion is vital to reduce exposure. However, data on skin absorption remain limited. We thus aim to characterize the skin permeation of three phthalates in a mixture, neat or in emulsion; di(2-ethylhexyl) phthalate (d4-DEHP), dibutyl phthalate (d4-DBP), and diethyl phthalate (d4-DEP), by comparing in vitro human skin (800 µm) permeation (24 hours) results using flow-through diffusion cells with urine results obtained from volunteers exposed to the same mixture applied to a forearm (40 cm2). Metabolites were analyzed in receptor fluids and urine. Phthalates crossed the skin barrier and metabolized into monoesters before elimination. Increased permeation was observed for phthalates in emulsion compared to neat substances, with polyethylene glycol (PEG) in the receptor fluid enhancing emulsion permeation, but not affecting neat substances. In vitro results mirrored in vivo findings: DEP showed rapid permeation (J: ∼2 ug/cm2/h) and urinary excretion peaking at six hours post-application, whereas DBP exhibited slower kinetics (J: ∼0.1 ug/cm2/h), with a urinary peak at 15-17 hours post-application. DEHP had minimal permeation (J: ∼0.0002 ug/cm2/h) with no observable urinary peak. These findings underscore the importance of comprehending phthalate skin absorption for effective exposure mitigation strategies.

Why are some individuals better at using negative attentional templates to suppress distractors? Exploration of interindividual differences in cognitive control efficiency.

Negative templates are based on foreknowledge of distractor features and can lead to more efficient visual search at the group level. However, large individual differences exist in the size of benefits induced by negative cues. The cognitive factors underlying these interindividual differences remain unknown. Previous research has suggested higher engagement of proactive control for negative templates compared to positive templates. We thus hypothesized that interindividual differences in proactive control efficiency may explain the large variability in negative cue benefits. A large data set made up of data from two previously published studies was reanalyzed (N = 139), with eye movements recorded in 36 participants. Individual proactive control efficiency was measured through reaction time (RT) variability. Participants with higher proactive control efficiency exhibited larger benefits after negative cues across two critical measures: Individuals with higher proactive control showed larger RT benefits following negative compared to neutral cues; similarly, individuals with higher proactive control exhibited lower first saccades to cued distractor items. No such relationship was observed for positive cues. Our results confirmed the existence of large interindividual differences in the benefits induced by negative attentional templates. Critically, we show that proactive control drives these interindividual differences in negative template use. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Generation of an Alagille Syndrome (ALGS) patient-derived induced pluripotent stem cell line (TRNDi036-A) carrying a heterozygous mutation (p.Cys693*) in the JAG1 gene.

Alagille syndrome (ALGS) is an autosomal dominant, multisystemic disorder due to haploinsufficiency in JAG1 or less frequently, mutations in NOTCH2. The disease has been difficult to diagnose and treat due to variable expression. The generation of this iPSC line (TRNDi036-A) carrying a heterozygous mutation (p.Cys693*) in the JAG1 gene provides a means of studying the disease and developing novel therapeutics towards patient treatment.

Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects: A Randomized Clinical Trial.

Importance: Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. Objectives: To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD. Design, Setting, and Participants: This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024. Intervention: Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age. Main Outcomes and Measures: The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment. Results: The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70). Conclusions and Relevance: In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex. Trial Registration: ClinicalTrials.gov Identifier: NCT02133573.

Distinct mechanisms of attentional suppression: exploration of trait factors underlying cued- and learned-suppression.

Attention allows us to focus on relevant information while ignoring distractions. Effective suppression of distracting information is crucial for efficient visual search. Recent studies have developed two paradigms to investigate attentional suppression: cued-suppression which is based on top-down control, and learned-suppression which is based on selection history. While both types of suppression reportedly engage proactive control, it remains unclear whether they rely on shared mechanisms. This study aimed to determine the relationship between cued- and learned-suppression. In a within-subjects design, 54 participants performed a cued-suppression task where pre-cues indicated upcoming target or distractor colors, and a learned-suppression task where a salient color distractor was present or absent. No significant correlation emerged between performance in the two tasks, suggesting distinct suppression mechanisms. Cued-suppression correlated with visual working memory capacity, indicating reliance on explicit control. In contrast, learned-suppression correlated with everyday distractibility, suggesting implicit control based on regularities. These results provide evidence for heterogeneous proactive control mechanisms underlying cued- and learned-suppression. While both engage inhibition, cued-suppression relies on deliberate top-down control modulated by working memory, whereas learned-suppression involves implicit suppression shaped by selection history and distractibility traits.

Optimizing Antidepressant Efficacy: Multimodal Neuroimaging Biomarkers for Prediction of Treatment Response.

Major depressive disorder (MDD) is a common and often severe condition that profoundly diminishes quality of life for individuals across ages and demographic groups. Unfortunately, current antidepressant and psychotherapeutic treatments exhibit limited efficacy and unsatisfactory response rates in a substantial number of patients. The development of effective therapies for MDD is hindered by the insufficiently understood heterogeneity within the disorder and its elusive underlying mechanisms. To address these challenges, we present a target-oriented multimodal fusion framework that robustly predicts antidepressant response by integrating structural and functional connectivity data (sertraline: R2 = 0.31; placebo: R2 = 0.22). Through the model, we identify multimodal neuroimaging biomarkers of antidepressant response and observe that sertraline and placebo show distinct predictive patterns. We further decompose the overall predictive patterns into constitutive network constellations with generalizable structural-functional co-variation, which exhibit treatment-specific association with personality traits and behavioral/cognitive task performance. Our innovative and interpretable multimodal framework provides novel insights into the intricate neuropsychopharmacology of antidepressant treatment and paves the way for advances in precision medicine and development of more targeted antidepressant therapeutics.

Narrative-Derived Indices of Metacognition among People with Schizophrenia: Associations with Self-Reported and Performance-Based Social Functioning.

Metacognitive functioning-which broadly encompasses the mental processes involved in thinking about the thinking of one's self and the thinking of others-is often impaired among individuals living with schizophrenia and may contribute to difficulties in social and interpersonal functioning. Although the majority of studies assessing metacognition among individuals with schizophrenia use standardized, laboratory-based measurements, an increasing number of studies have measured metacognitive capacity using natural language produced by individuals living with mental illness. At the same time, less is known about how language-derived indices of metacognitive function relate to key social outcomes among people with schizophrenia. The primary objective of this study was to employ a validated language coding system (the Metacognition Assessment Scale, Abbreviated; MAS-A) to assess metacognitive functioning from the spoken life narratives of individuals with schizophrenia (n = 32) and community controls (n = 15). Among individuals with schizophrenia, we also examined the associations between language-derived metacognition and measures of self-reported and performance-based social functioning. Our results suggest that most aspects of metacognition in our sample were not significantly diminished in people with schizophrenia compared to community controls. Unexpectedly, the MAS-A subscale related to one's ability to master psychological difficulties was rated higher among individuals with schizophrenia. Further, our results suggest that among people with schizophrenia, higher metacognitive functioning in the domain of self-reflectivity was associated with poorer self-reported social functioning, while a greater metacognitive awareness of other individuals' minds was associated with better scores on aspects of performance-based social functioning. Collectively, these results underscore the utility of assessing metacognitive functioning via life-story narratives to understand social outcomes and highlight possible aspects of resiliency among individuals who have experienced a serious mental illness.

Air Pollution and Primary DNA Damage among Zagreb (Croatia) Residents: A Cross-Sectional Study.

More than eight million premature deaths annually can be attributed to air pollution, with 99% of the world's population residing in areas below recommended air quality standards. Hence, the present study aimed to examine the association between primary DNA damage and air pollution data among 123 participants enrolled between 2011 and 2015 in Zagreb, Croatia. While most measured air pollutants adhered to regulatory limits, benzo[a]pyrene concentrations bound to PM10 exceeded them. Factorial analysis narrowed down air pollution data to four exposure factors (particulate matter, two metal factors, and other pollutants). Despite the absence of significant positive associations between modeled air pollution exposure factors and comet assay descriptors (tail length, tail intensity, tail moment, and highly damaged nuclei), the critical health implications of air pollution warrant further investigations, particularly with biomarkers of exposure and different biomarkers of effect in populations facing air pollution exposure.

Ecological countermeasures to prevent pathogen spillover and subsequent pandemics.

Substantial global attention is focused on how to reduce the risk of future pandemics. Reducing this risk requires investment in prevention, preparedness, and response. Although preparedness and response have received significant focus, prevention, especially the prevention of zoonotic spillover, remains largely absent from global conversations. This oversight is due in part to the lack of a clear definition of prevention and lack of guidance on how to achieve it. To address this gap, we elucidate the mechanisms linking environmental change and zoonotic spillover using spillover of viruses from bats as a case study. We identify ecological interventions that can disrupt these spillover mechanisms and propose policy frameworks for their implementation. Recognizing that pandemics originate in ecological systems, we advocate for integrating ecological approaches alongside biomedical approaches in a comprehensive and balanced pandemic prevention strategy.

Palaeoatmosphere facilitates a gliding transition to powered flight in the Eocene bat, Onychonycteris finneyi.

The evolutionary transition to powered flight remains controversial in bats, the only flying mammals. We applied aerodynamic modeling to reconstruct flight in the oldest complete fossil bat, the archaic Onychonycteris finneyi from the early Eocene of North America. Results indicate that Onychonycteris was capable of both gliding and powered flight either in a standard normodense aerial medium or in the hyperdense atmosphere that we estimate for the Eocene from two independent palaeogeochemical proxies. Aerodynamic continuity across a morphological gradient is further demonstrated by modeled intermediate forms with increasing aspect ratio (AR) produced by digital elongation based on chiropteran developmental data. Here a gliding performance gradient emerged of decreasing sink rate with increasing AR that eventually allowed applying available muscle power to achieve level flight using flapping, which is greatly facilitated in hyperdense air. This gradient strongly supports a gliding (trees-down) transition to powered flight in bats.

Metal and oxidative potential exposure through particle inhalation and oxidative stress biomarkers: a 2-week pilot prospective study among Parisian subway workers.

OBJECTIVE: In this pilot study on subway workers, we explored the relationships between particle exposure and oxidative stress biomarkers in exhaled breath condensate (EBC) and urine to identify the most relevant biomarkers for a large-scale study in this field. METHODS: We constructed a comprehensive occupational exposure assessment among subway workers in three distinct jobs over 10 working days, measuring daily concentrations of particulate matter (PM), their metal content and oxidative potential (OP). Individual pre- and post-shift EBC and urine samples were collected daily. Three oxidative stress biomarkers were measured in these matrices: malondialdehyde (MDA), 8-hydroxy-2'deoxyguanosine (8-OHdG) and 8-isoprostane. The association between each effect biomarker and exposure variables was estimated by multivariable multilevel mixed-effect models with and without lag times. RESULTS: The OP was positively associated with Fe and Mn, but not associated with any effect biomarkers. Concentration changes of effect biomarkers in EBC and urine were associated with transition metals in PM (Cu and Zn) and furthermore with specific metals in EBC (Ba, Co, Cr and Mn) and in urine (Ba, Cu, Co, Mo, Ni, Ti and Zn). The direction of these associations was both metal- and time-dependent. Associations between Cu or Zn and MDAEBC generally reached statistical significance after a delayed time of 12 or 24 h after exposure. Changes in metal concentrations in EBC and urine were associated with MDA and 8-OHdG concentrations the same day. CONCLUSION: Associations between MDA in both EBC and urine gave opposite response for subway particles containing Zn versus Cu. This diverting Zn and Cu pattern was also observed for 8-OHdG and urinary concentrations of these two metals. Overall, MDA and 8-OHdG responses were sensitive for same-day metal exposures in both matrices. We recommend MDA and 8-OHdG in large field studies to account for oxidative stress originating from metals in inhaled particulate matter.

Perception-Action Approach Versus Standard Care for Infants With Congenital Muscular Torticollis: A Pilot Single-Blind Randomized Controlled Trial.

OBJECTIVE: The purposes of this pilot study were to compare short-term outcomes of the Perception-Action Approach (P-AA) and standard care based on 5 components of first-choice interventions listed in the congenital muscular torticollis (CMT) clinical practice guideline. Changes in postural alignment, symmetrical use of both sides of the body during movement and play, gross motor development, and behavior observed during therapy were considered. METHODS: Thirty-two participants were enrolled in a 2-group (P-AA and standard care) randomized, single-blind trial with pre-posttest measures. Participants were infants with CMT, age range 5 to 35 weeks at enrollment. Outcome measures administered at initial and final evaluations included still photography, arthrodial goniometry, Muscle Function Scale, Alberta Infant Motor Scale, and Functional Symmetry Observation Scale. Participants in both groups attended 3 intervention sessions. Their behavior exhibited during therapy was compared using the Therapy Behavior Scale Version 2.2. RESULTS: Data collection was interrupted by the COVID-19 pandemic lockdown. Twenty-four infants completed the study (10 in P-AA and 14 in the standard care group). There were no significant differences between the groups in performance at initial and final evaluations. Both groups improved on most outcome measures. The P-AA group made greater gains on the Functional Symmetry Observation Scale, and the Therapy Behavior Scale Version 2.2 scores were higher in the P-AA group; however, these results did not reach significance. CONCLUSION: Results suggest that similar short-term outcomes may be obtained in infants with CMT undergoing P-AA and standard care interventions. Definitive conclusions regarding the efficacy of the P-AA in infants with CMT cannot be made at this time. Nevertheless, the pilot findings provide valuable preliminary data for a future efficacy trial, which will require funding. IMPACT: This was the first randomized controlled trial to provide evidence for use of P-AA intervention in infants with CMT. LAY SUMMARY: Compared to standard treatment, the Perception-Action Approach (P-AA) provided similar short-term benefits to infants with congenital muscular torticollis. The P-AA group participants demonstrated higher symmetry and behavior scores, which needs to be confirmed in a larger future study.

The association between safety climate and noncombat injury events among United States Air Force workers.

INTRODUCTION: Work-related injuries are a common lagging safety indicator whereas safety climate assessments can help identify constructs serving as leading indicators. The National Institute for Occupational Safety and Health (NIOSH) partnered with the U.S. Department of the Air Force (DAF) Safety Center to examine the association between perceptions of safety climate survey constructs and the number of injury events within the DAF workforce. METHODS: The DAF administers voluntary, anonymous, occupation-specific safety climate surveys to DAF workers using the internal Air Force Combined Mishap Reduction System (AFCMRS). Survey responses from 2014 to 2018 provided by DAF workers and injury events in maintenance, support, and operations occupations were shared with NIOSH. Exploratory Factor Analysis revealed five constructs: Leadership and Communication; Organizational Safety Priority; Error Management; Resource Adequacy; and Deployment/Official Travel Impact. Squadron-level analysis included bivariate correlations and estimated Rate Ratios (RRs). RESULTS: 1,547 squadrons administered the survey, averaging 144 workers and 15.8 reportable injuries per squadron. Higher (more favorable) squadron-level construct scores were consistently correlated with fewer reported injuries (p < 0.001). Controlling for the number of workers, RRs revealed significant reductions in injury rates with each one-unit increase in responses: Leadership and Communication RR = 0.40 (95%CI: 0.32-0.48); Organizational Safety Priority RR = 0.50 (95%CI: 0.40-0.64); Error Management RR = 0.37 (95%CI: 0.30-0.47); Deployment/Official Travel Impact RR = 0.36 (95%CI: 0.29-0.45). Resource Adequacy revealed a non-significant lower injury rate RR = 0.87 (95%CI: 0.73-1.04). CONCLUSIONS: This unique study quantified safety climate and the association with injuries across a multi-year period. While safety climate measurements may be limited by frequent turnover and the self-reported, voluntary, anonymous nature of AFCMRS, the strength of this study is in the census of injuries. PRACTICAL APPLICATIONS: Future research should include longitudinal analyses to examine the impact on injuries when squadron leaders are provided feedback on safety climate survey results.

Project Building Bridges: A Framework for Preparing Highly Qualified Speech-Language Pathologists to Serve Culturally and Linguistically Diverse Students With Augmentative and Alternative Communication Needs.

PURPOSE: Project Building Bridges was funded by the U.S. Department of Education Office of Special Education Programs to address the shortage of speech-language pathologists qualified to serve students with complex communication needs who benefit from augmentative and alternative communication (AAC) and are culturally and linguistically diverse. The purpose was to train future speech-language pathologists in culturally responsive AAC practices through coursework and fieldwork in AAC integrated into the Master of Science degree in Speech, Language and Hearing Sciences. METHOD: Fifty-seven graduate students completed the project. The scholars' curriculum consisted of two AAC courses, both on-campus and externship AAC clinical practicum experiences to provide services to multicultural and linguistically diverse students, a U.S. or international service-learning opportunity, and cumulative portfolio presentations. RESULTS: Mixed-methods outcome measures consisted of four sets of pre- and postsurveys and qualitative feedback from exit interviews to assess changes in graduate student competencies. Significant differences were demonstrated between scholars' pre- and post-assessments of confidence ratings. Significant differences were also demonstrated in both scholars' and school mentors' pre- and post-assessments of competency ratings. No significant differences were found between evaluations of AAC preparation by Clinical Fellowship (CF) candidates and their CF mentors at 1 year postgraduation. CONCLUSIONS: Project Building Bridges provides a framework for preparing highly qualified speech-language pathologists to serve culturally and linguistically diverse students who benefit from AAC as evidenced by pre- and postsurvey results. The project can serve as a model for other university programs in the development of preservice preparation programs focusing on culturally and linguistically diverse students with AAC needs.